There are currently no animal models of primary uveal melanoma, a potentially blinding as well as lethal condition. There are two major reasons for developing an animal model of primary uveal melanoma: (1) to permit the pathologic correlation of the clinically observed stages of tumor development, impossible in the patient because of the difficulty in obtaining representative choroidal biopsies without significant ocular morbidity, and (2) to permit the comparison and evaluation of existing diagnostic and therapeutic strategies and the development of new techniques that can be tested in a model before coming to clinical trial; the limited numbers of new uveal melanoma patients seen each year make it difficult to prospectively evaluate and compare current and emerging diagnostic techniques and treatment strategies and even the currently funded Collaborative Ocular Melanoma Study will take at least ten years to complete. Presently, the most popular animal model of uveal melanoma is transplantation of Greene hamster cutaneous melanoma into the rabbit eye. Although this model has permitted the evaluation of experimental therapeutic techniques, this transplantation-based model cannot be used to study the development of a melanoma from the normal choroid and is not satisfactory for studying the immunologic responses to uveal melanoma. However, the popularity of the Greene melanoma transplantation model has led to a wealth of experience in manipulating the rabbit eye to study diagnostic and therapeutic approaches to intraocular tumors and the development of a model of primary uveal melanoma in the rabbit would be highly desirable. Spontaneous primary uveal melanoma in the rabbit has been reported but is extremely rare. The chemical carcinogen, 7,12-dimethylbenz(a)-anthracene (DMBA) has been used repeatedly to induce models of cutaneous melanoma in laboratory animals, including animals considered resistant to the induction of melanoma. This laboratory has developed a technique to permit chronic exposure of the rabbit choroid to DMBA. Responding to the Report of the Retinal and Choroidal Disease Panel (Vision Research: A National Plan, 1983-1987, which assigned a high priority to the development of animal models of choroidal melanoma and specifically called for the induction of melanoma using chemical carcinogens, this laboratory proposes the development of a model of primary uveal melanoma in the rabbit to correlate the natural history of a primary uveal melanoma with pathology and to permit the evaluation of established and experimental diagnostic and therapeutic techniques.